J Neurosurg Pediatrics 1:330–333, 2008
Postoperative hemicerebellar inflammation mimicking recurrent tumor after resection of a medulloblastoma Case report SASKIA E. LUIJNENBURG, M.D.,1 PATRICK W. HANLO, M.D., PH.D.,2 K. SEN HAN, M.D., PH.D.,2 WIJNANDA A. KORS, M.D.,3 THEO D. WITKAMP, M.D.,4 AND JONATHAN I. M. L. VERBEKE, M.D.5 Departments of 1Pediatrics and 2Pediatric Neurosurgery, Wilhelmina Children’s Hospital/University Medical Center Utrecht; 4Department of Radiology, University Medical Center Utrecht; and Departments of 3Pediatric Oncology/Hematology and 5Radiology, VU Medical Center, Amsterdam, The Netherlands
PThe authors present the case of a 4-year-old boy in whom a medulloblastoma in the left cerebellar hemisphere was successfully resected with no signs of residual tumor on the postoperative magnetic resonance (MR) images. A second MR imaging study performed 1 month after surgery demonstrated an extensive, contrast-enhancing lesion in the left cerebellar hemisphere, which simulated massive recurrent tumor, and repeated surgery was considered. A third postoperative MR imaging study, performed for evaluation of the craniospinal axis 10 days after the second postoperative study, still showed some contrast enhancement in the left cerebellar hemisphere, but the lesion had almost disappeared. Postoperative hemicerebellar inflammation seemed to be the most likely explanation. This case illustrates that early postoperative inflammation can mimic recurrent tumor on MR images obtained after resection of a medulloblastoma and caution should be taken in interpreting such images. Clinical history, neurological examination, laboratory findings, and repeated MR imaging studies can be helpful in evaluating the patient accurately. (DOI: 10.3171/PED/2008/1/4/330) KEY WORDS • cerebellitis • magnetic resonance imaging • medulloblastoma • postoperative inflammation • recurrent disease
is a highly malignant tumor of the posterior fossa that is predominantly seen in children and accounts for 25% of all pediatric intracranial tumors.16 Magnetic resonance imaging is frequently used to determine accurate staging preoperatively and for early detection of recurrent disease during followup. Medulloblastomas appear hypointense on T1-weighted MR images and demonstrate heterogeneous signal intensity on T2-weighted images. The mass usually enhances upon administration of a contrast agent, but this finding may be variable.3,23 Recurrence of medulloblastoma is unfortunately very common. Most recurrent disease in children develops in the first 2 years after initial treatment and usually in the posterior fossa.14,17,22,24 Medulloblastomas frequently disseminate along the cerebrospinal fluid pathways, and evidence of leptomeningeal metastatic spread is present in up to 33% of all cases at the time of diagnosis.3,24 The prognosis of medulloblastoma has improved signifi-
M
EDULLOBLASTOMA
Abbreviations used in this paper: ICP = intracranial pressure; MR = magnetic resonance.
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cantly over the past several decades due to improvements in neurosurgical technique, radiation therapy of the entire craniospinal axis, and adjuvant chemotherapy, with 5-year survival rates between 50 and 70% in most studies and . 80% in some reports.14 We report here the case of a 4-year-old boy in whom a medulloblastoma in the left cerebellar hemisphere was successfully resected and in whom MR imaging demonstrated an extensive, contrast-enhancing lesion in the left cerebellar hemisphere 1 month after surgery, before initiation of adjunctive treatment. Case Report Presentation and Examination. This 4-year-old boy presented to us with symptoms of raised ICP, consisting of progressive headaches for 1 month and vomiting, which started on the day of evaluation in our hospital. His head circumference was at the 50th percentile and neurological examination revealed only a mild ataxia of his left hand. No other neurological deficits could be observed. J. Neurosurg.: Pediatrics / Volume 1 / April 2008
Postoperative inflammation mimicking recurrent medulloblastoma Neuroimaging Findings. An MR imaging study revealed a heterogeneous mass with a cystic component in the left cerebellar hemisphere with compression of the fourth ventricle (Fig. 1). The tumor was hypointense on T1-weighted images, inhomogeneous on T2-weighted images, and inhomogeneously contrast enhancing after the administration of gadolinium. The most likely diagnosis at that time was a juvenile pilocytic astrocytoma. The MR images showed no other lesions in the brain or the spinal cord. Operation and Histopathological Findings. An external ventricular drain was placed 2 days before tumor surgery because of progressive symptoms of raised ICP. Two days later, a posterior fossa craniotomy was performed, in which the tumor turned out to be not well delineated. No clear demarcation between tumor tissue and surrounding brain tissue was evident, but eventually a near-total resection was performed. Histopathological examination revealed an undifferentiated, embryonic tumor, which was diagnosed as a medulloblastoma. An atypical teratoid rhabdoid tumor was also considered at first, but this diagnosis was excluded on the basis of the examination, in which the findings of the histological analysis in particular did not correspond with a diagnosis of atypical teratoid rhabdoid tumor. Postoperative Course. Postoperative neurological examination showed ataxia of the left arm and left hand, which improved after ~ 2 days. There were no other neurological deficits. A postoperative MR imaging study, performed 4 days after surgery, showed no signs of residual tumor (Fig. 2). The external ventricular drain could be removed 5 days after surgery, and there were no symptoms of recurrent raised ICP. Our patient was scheduled to receive adjunctive treatment according to the SIOP PNET 4 protocol. In this protocol, patients are treated with radiotherapy and chemotherapy, with the provision that radiotherapy should start # 40 days after surgery. Prior to start of the planned treatment, however, the early postoperative MR imaging study was reviewed in the center where the adjunctive treatment was to take place. A question arose as to whether there was some residual tumor after all. Therefore, a second postoperative MR imaging
study was performed 1 month after surgery, which revealed an extensive lesion in the left cerebellar hemisphere (Fig. 3). The lesion was hypointense on T1-weighted images, hyperintense on T2-weighted images, and showed dural, leptomeningeal, and parenchymal contrast enhancement after administration of gadolinium. The images also revealed cerebellar swelling, demonstrating a deformed fourth ventricle. These findings were thought to represent massive recurrent tumor, and a second operation was considered. Neurological examination revealed no abnormalities at this time and the patient experienced no symptoms of raised ICP. Because of the possible rapid recurrence of the tumor, the child was referred back to our hospital and a third postoperative craniospinal MR imaging study was performed 10 days after the second postoperative imaging study to evaluate the possibility of metastatic lesions in the spinal cord. To our surprise, this third postoperative neuroimaging study did not show the extensive lesion in the left cerebellar hemisphere that had been noted on the images obtained just 10 days before (Fig. 4). There was still some contrast-enhancement in the left cerebellar hemisphere, but it was markedly reduced compared to what was evident on images from the
FIG. 1. Preoperative MR images showing a tumor in the left cerebellar hemisphere. Left: Axial T1-weighted image showing the tumor as hypointense. Compression of the fourth ventricle is present. Right: Axial image obtained after gadolinium administration showing inhomogeneous contrast enhancement.
FIG. 3. Axial MR images obtained in the second postoperative imaging study, 1 month after surgery, showing an extensive lesion in the left cerebellar hemisphere, which is hypointense on the T1weighted image (left) and shows enhancement after administration of gadolinium (right). Note the deformation of the fourth ventricle.
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FIG. 2. Postoperative axial MR images obtained 4 days after surgery showing a large resection cavity is present in the left cerebellar hemisphere (left) and no signs of residual tumor after gadolinium administration (right).
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FIG. 4. Axial T1-weighted images obtained with (left) and without (right) gadolinium 10 days after the images in Fig. 3. There is no longer any deformation of the fourth ventricle. Some areas of contrast enhancement are still evident in the gadolinium-enhanced image, but they are markedly reduced in comparison with the previous study.
second postoperative study, and could be described as normal postoperative enhancement. The form and size of the fourth ventricle had returned to normal and the brain shift had disappeared. No spinal metastatic lesions were found. Neurological examination revealed no abnormalities. The 3 sets of postoperative MR images were then once again evaluated by the neuroradiologists. Because the most recent MR images showed that the lesion had almost disappeared, recurrent tumor was excluded. Similarly, an ischemic lesion seemed improbable because neuroimaging findings had improved so much and because our patient showed no signs of cerebellar dysfunction. Therefore, postoperative inflammation was thought to be the most likely explanation. Our patient then started with his adjunctive treatment. An MR imaging study performed 14 months later revealed no abnormalities. Discussion Postoperative MR imaging with contrast enhancement is the procedure of choice for assessing the presence and extent of residual tumor after initial resection of medulloblastoma.17 Studies have been performed to determine which enhancement patterns on MR images obtained after intracranial surgery are most likely to represent benign postoperative changes and which patterns are suspect for residual or recurrent tumor. The time course of normal postoperative changes has also been described and is important in determining the optimal time for a postoperative MR imaging study. Contrast enhancement in the postoperative brain is thought to be the result of several pathophysiological changes, such as local disruption of the blood–brain barrier, surgical injury, direct extravasation of contrast material from injured tissue, and neovascularization.6,10,19,20 Enhancement Patterns on Postoperative MR Images
Meyers et al.17 characterized the contrast-enhancing MR imaging findings in 48 patients (mean age 8.3 years) after resection of medulloblastomas. The authors concluded that pia–arachnoid or focal nodular brain contrast enhancements 332
were the most frequent patterns associated with recurrent tumor. Linear enhancement at the surgical margin was observed in most patients without recurrent disease within the first 3 weeks following surgery. Dural enhancement was observed both in patients with and in those without recurrent disease. Sato et al.20 described the MR imaging findings after brain surgery in 95 patients (mean age 31.8 yrs) without neoplasms. They found that parenchymal enhancement of the surgical margin was present from 20 hours to 29 days after surgery and showed a progressive increase during the first week. The early pattern (Days 0–5) was thin linear enhancement, and the later pattern (Days 6–29) was thick linear or nodular enhancement, which could be mistaken for residual or recurrent tumor. Surgical margin enhancement was absent after Day 30. On the basis of these findings, the authors advise performing an MR imaging study during the first 5 postoperative days because this is the period in which normal postoperative enhancement is least likely to simulate tumor. Dural enhancement was seen on almost all of the postoperative images in their study. It was moderate or prominent in the early postoperative images and had decreased to a minimal or moderate level during the first postoperative year. Several other authors have also identified thin linear enhancement patterns as a reflection of benign changes or changes secondary to surgical trauma, whereas the enhancement patterns in cases of residual or recurrent tumors have been reported to be more likely to be thick linear–nodular.2,6,7,10 Inflammation and Infection
In our patient, recurrent tumor and ischemia were excluded after the third MR imaging study, and postoperative inflammation or infection was considered as an explanation for the enhancing lesion. The MR imaging findings in acute cerebellitis are typically bilateral hemispheric hyperintensities on T2-weighted sequences, with or without gadolinium enhancement.1,4,5,9,11 There are often signs of cerebellar swelling, too. Involvement of only a single hemisphere is less frequently encountered.4,12,13,21 Jabbour et al.13 described a case of a 13-yearold girl in whom the MR imaging scan revealed a lesion in the right cerebellar hemisphere. It mimicked a cerebellar tumor, but a biopsy showed a heavy lymphocytic infiltration, suggestive of cerebellar leptomeningitis. Acute cerebellitis usually manifests as truncal ataxia, headaches, nystagmus, tremor, and myoclonic jerks.9,11,13 This disorder typically occurs after a viral infection, but in many cases no specific virus is isolated.1,4,5,9,11,12,13 Treatment is symptomatic and/or antiviral in the majority of cases.4 When the enhancing lesion was first seen on the MR images obtained in our patient, postoperative inflammation or infection was not considered at first because our patient did not show any symptoms of cerebellar dysfunction or raised ICP. The patient’s history revealed no signs of a viral infection in the previous weeks either. Additional imaging modalities, such as MR spectroscopy, diffusion or perfusion imaging, or nuclear medicine studies, were not used in this case, but might be of use in trying to differentiate recurrent tumor from vascular or inflammatory reaction. Additional tests, such as polymerase chain reaction studies for viruses or evaluating infectious parameters such as J. Neurosurg.: Pediatrics / Volume 1 / April 2008
Postoperative inflammation mimicking recurrent medulloblastoma C-reactive protein, were not performed. Three days before the MR imaging study that showed the extensive lesion, the patient underwent a lumbar puncture as part of the postoperative staging protocol. Analysis of the cerebrospinal fluid showed a slightly increased leukocyte count (75/ml), which could very well have been caused by the recent surgery. Other parameters, including total protein and glucose levels, were not abnormal. Histopathological examination did not reveal malignant cells and routinely performed serological tests showed no abnormalities. The case we describe does not completely match the definition of acute cerebellitis, mostly because our patient did not show any symptoms of cerebellar dysfunction and had no recent history of a viral infection. Therefore postoperative hemicerebellar inflammation, as an explanation for the temporary MR imaging abnormalities, seems the most likely diagnosis in our patient, but the cause of the inflammatory reaction remains unclear. Several reports show that an inflammatory reaction can be caused by hemostatic material or other foreign materials left in the resection cavity at the time of surgery. In our patient, some materials were left in the resection cavity during surgery, namely fibrin glue (Tissuecol) to cover the surgical area and a dura substitute (Lyoplant) to repair the defect in the dura mater. Nevertheless, foreign body granulomas induced by such materials usually occur in a later time course, and such a causal mechanism therefore seems less probable in our patient.8,15,18 Kothbauer et al.15 described 3 children who had undergone surgery for the treatment of primitive neuroectodermal tumors and in whom MR images revealed lesions suspect for recurrent disease 2–7 months after the initial surgery. The children underwent repeated surgery, and histological analysis of the resected material revealed foreign body granulomas, with Gelfoam or Surgicel as the underlying cause. In our case, we could not perform any such histological analysis because a second operation was not performed, and the cause of the inflammatory reaction will therefore remain unclear.
5. 6.
7. 8. 9. 10. 11. 12.
13. 14. 15.
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Conclusions Postoperative inflammation evidenced by such massive MR imaging abnormalities as seen in our patient 1 month after surgery can be a serious pitfall in the treatment of a malignant posterior fossa tumor and has not previously been reported in the literature. Our case illustrates that postoperative inflammation after resection of a medulloblastoma can mimic recurrent tumor. Appropriate timing of postoperative MR imaging is important, and caution should be applied in interpreting such images. Clinical history, neurological examination, laboratory findings, and subsequent MR imaging studies can be helpful in evaluating the patient’s condition accurately.
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Manuscript submitted June 15, 2007. Accepted December 11, 2007. Address correspondence to: Patrick W. Hanlo, M.D., Ph.D., Department of Neurosurgery, KC.03.063.0, University Medical Center Utrecht, P.O. Box 85090, 3508 AB Utrecht, The Netherlands. email:
[email protected].
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